Expression of melatonin receptor (MT1) and interaction between melatonin and estrogen in endometrial cancer cell line.
OBJECTIVE
To determine the receptor subtypes of melatonin in estrogen receptor-positive endometrial cancer cell line, Ishikawa, and the influence of melatonin on chemosensitivity.


METHODS
To confirm the subtype of melatonin on Ishikawa cells, cells were treated with melatonin alone and with antagonists against melatonin receptor luzindole and 4-phenyl-2-propionamidotetralin (4-P-PDOT). Expression of MT1/MT2 mRNA was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Immunocytochemistry of MT1/MT2 was also performed. The effect of melatonin against expression of MT1, MT2, and ERalpha-receptors mRNA was compared with RT-PCR. To determine whether melatonin enhances the effect of anticancer agents, chemosensitivity test was performed with or without melatonin.


RESULTS
Our study revealed that Ishikawa cells express MT1 by both RT-PCR and immunocytochemistry. In contrast, expression of MT2 mRNA was not found. Furthermore, ERalpha mRNA expression was attenuated at melatonin level of 1 x 10(-9) M. Chemosensitivity test revealed that melatonin enhanced anti-tumor effects of paclitaxel among anticancer drugs tested.


CONCLUSIONS
Based on the above results, MT1 receptor, but not MT2, is expressed in Ishikawa cells. It was also revealed that the cytostatic effect of melatonin is partly an action mediated by MT1 receptor, and attenuation of ERalpha expression was predicted as the mechanism of action. Clinical application of melatonin to biochemotherapy might be also expected.
Watanabe
Mari
M
Department of Obstetrics and Gynecology, St Marianna University School of Medicine, Kanagawa, Japan.
Kobayashi
Yoichi
Y
Takahashi
Noriyuki
N
Kiguchi
Kazushige
K
Ishizuka
Bunpei
B
D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D008550:Melatonin / Q000378:metabolism*; D044122:Receptor, Melatonin, MT1 / Q000096:biosynthesis* / Q000235:genetics; D044123:Receptor, Melatonin, MT2 / Q000096:biosynthesis / Q000235:genetics
D004967:Estrogens; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin